Cholesterol levels in blood are related to the risk factors associated with coronary heart disease. Efforts have been made to determine cholesterol level in blood of patients but none have provided a rapid and accurate procedure.
Considerable effort has been placed on trying to identify risk factors associated with coronary heart disease (CHD). The clinical laboratory has had its share of work in this effort with respect to lipoprotein analysis. Most laboratories offer cholesterol and triglyceride analysis, but recent studies are showing these tests to be about as obsolete as total lipid analysis. Electrophoresis of plasma lipoproteins gave some impetus to the presumptive pheno-typing of patients, but this testing tended to focus on abnormalities of (low density lipoproteins) (LDL or .beta. lipoprotein) and very low density lipoproteins (VLDL or pre-.beta. lipoproteins) with very little interest shown in the high density lipoprotein (HDL or .alpha. lipoproteins). Clinical chemists are beginning to focus on some of the important epidemiological studies that have shown the probable value of HDL cholesterol estimations and show in pragmatic terms how this test can be incorporated into every routine clinical laboratory.
One of the earliest reports associating HDL with CHD was that of Barr et al, Am.J.Med. 11,480 (1951). In this study, the researchers made the observation that healthy men had higher HDL levels than did men with CHD. This finding was subsequently confirmed in many other studies. More recent publications involving large numbers of patient values have shown unequivocally the value of fractionating total cholestrol values into HDL and VLDL and LDL cholesterol.
HDL is a lipoprotein synthesized by the liver. One proposed mechanism of its action which fits with clinical data is that HDL is the transport mechanism which removes cholesterol from the peripheral tissues and carries it to the liver for catabolism. Thus, if the HDL levels are normal or high, then there is efficient removal of cholesterol which lowers the tissue pool and lessens the risk of deposition of cholesterol. Conversely, if the HDL levels are low, then there is inefficient removal of cholesterol and the subsequent risk of CHD is higher. Several observations lend support to this hypothesis.
1. In Tangier disease (deficiency of HDL) all patients have excessive deposition of cholesterol esters in the blood vessels.
2. Women have higher HDL levels than men and a lesser risk of developing CHD.
3. Blacks have higher HDL levels than whites with a lesser risk of developing CHD.
4. Children have higher HDL levels than adults, black children have higher levels than white children.
5. The prevalence of CHD in men aged 50-69 was double in the very low HDL groups compared to those above the population mean.
All of these studies were based on epidemiological data concerned with the prevalence of CHD. A few studies have now been conducted as prospective studies with respect to the incidence of the disease. In a report published in 1966 researchers suggested that the incidence of CHD was higher in young men with low HDL levels. A similar report was published in a study of middle aged men.
One of the most recent reports on the relationship between CHD and fasting plasma lipids was assessed by a case-controlled study in five populations with a total of 6,859 men and women of black, white and Japanese ancestry. In each major study, a statistically significant inverse relationship was found with CHD: it was found in most age-sex-race specific groups. These authors concluded that the "virtue of partitioning total cholesterol in assessing CHD risk is unequivocally demonstrated." HDL cholesterol has a negative correlation with CHD whereas LDL and VLDL cholesterol have a positive correlation with CHD. Hence, the "Total cholesterol (HDL & LDL & VLDL) must be a less sensitive indicator of risk than an appropriately weighted algebraic sum." Castelli et al. Circulation, 55 767 (1977).